Model for the kinetics of imipramine and its metabolites in adolescents.
A kinetic model for imipramine (IMI) has been developed, based upon a study of 16 teenagers who received IMI 4-5 mg/kg/day for treatment of a major depressive disorder. Serial measurements of plasma concentrations of IMI, desmethylimipramine (DMI), 2-hydroxy-IMI, and 2-hydroxy-DMI were made. Mean residence times, volumes of distribution, clearances of IMI and DMI, and rate constants for formation and elimination of the hydroxy metabolites were determined from a multicompartment model fitted to the concentration-time data. Mean residence time for DMI was significantly longer than for IMI (47.1 +/- 21.2 vs. 13.4 +/- 4.8 h, p less than 0.001). A different volume of distribution for IMI and DMI was not supported by the data. Clearance of DMI was considerably slower than that of IMI (0.67 +/- 0.45 vs. 2.18 +/- 1.33 l(kg.h), p less than 0.001). A statistically significant increase in mean residence time with increasing age during adolescence was found (r = 0.57, p less than 0.05).
Dell
R B
RB
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Hein
K
K
Ramakrishnan
R
R
Puig-Antich
J
J
Cooper
T
T
D000293:Adolescent; D003891:Desipramine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical
C033803:2-hydroxyimipramine; D007099:Imipramine; D003891:Desipramine; C028653:2-hydroxydesipramine